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Expressing Surface Proteins to Target Cancer Cells

Expressing Surface Proteins to Target Cancer Cells. Joe and Bobby. Goal. To localize medicine-carrying bacteria to cancer cells. Cancer antigens. Tumor cells express surface molecules mostly specific to cancer = antibody targets Detection of tumors

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Expressing Surface Proteins to Target Cancer Cells

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  1. Expressing Surface Proteins to Target Cancer Cells Joe and Bobby

  2. Goal • To localize medicine-carrying bacteria to cancer cells

  3. Cancer antigens • Tumor cells express surface molecules mostly specific to cancer = antibody targets • Detection of tumors • Antibody-dependent cellular cytotoxicity (ADCC) • Payload delivery http://www.antibody.com

  4. Current Antibody-based Cancer Therapy • Herceptin (trastuzumab) • Monoclonal antibody that binds to HER2/neu receptor in early-stage breast cancer cells • Rituxan (rituximab) • Antibody that binds to CD20, a protein expressed by B cells (normal & malignant) • Used to combat B cell non-Hodgkin’s lymphoma, B-cell leukemias

  5. Erbitux (cetuximab) • Attaches to external growth factor receptor (EGFR), mediates ADCC • $30k for 8 weeks

  6. Purpose of Our Antibody • Cancer-seeking antibody is expressed on surface of bacteria carrying a payload (medicine)

  7. Process • Discover effective monoclonal antibody • Find gene sequence • Transform gene into bacteria • Bacteria then expresses antibody

  8. 1. Discover effective antibody • Find cancer cells that express exclusive antigens • Steps • Immunization (mice, rats): generate antibody response • Immortalize antibody response as hybridomas • Create monoclonal antibodies from hybridomas; screen antibodies http://www.antibody.com

  9. 2. Find gene sequence • Identify gene that codes for the antibody 2.5. Alternatively • Use an antibody that has already been identified/matched to type of cancer cell

  10. 3. Transform gene into bacteria • Standard procedures • Listeria or E. coli

  11. 4. Bacteria then expresses antibody • Bacteria (which holds a payload of medicine/toxins/whatever) expresses cancer-specific antibody • Cancer cells take up bacteria

  12. Interesting? • Monoclonal antibody therapy of cancer http://www.nature.com/nbt/journal/v23/n9/full/nbt1137.html • Antibody Solutions Inc (www.antibody.com) based in Mountain View

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